|Title||Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial.|
|Publication Type||Journal Article|
|Year of Publication||2011|
|Authors||Krishnan, A, Pasquini, MC, Logan, B, Stadtmauer, EA, Vesole, DH, Alyea, E, Antin, JH, Comenzo, R, Goodman, S, Hari, P, Laport, G, Qazilbash, MH, Rowley, S, Sahebi, F, Somlo, G, Vogl, DT, Weisdorf, D, Ewell, M, Wu, J, Geller, NL, Horowitz, MM, Giralt, S, Maloney, DG|
|Corporate Authors||Blood Marrow Transplant Clinical Trials Network (BMT CTN)|
|Date Published||2011 Dec|
|Keywords||Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Dexamethasone, Disease-Free Survival, Female, Graft vs Tumor Effect, Hematopoietic Stem Cell Transplantation, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Multiple Myeloma, Myeloablative Agonists, Proportional Hazards Models, Risk Assessment, Risk Factors, Survival Rate, Thalidomide, Time Factors, Transplantation, Autologous, Transplantation, Homologous, Treatment Outcome, United States, Young Adult|
BACKGROUND: Autologous haemopoietic stem-cell transplantation (HSCT) improves survival in patients with multiple myeloma, but disease progression remains an issue. Allogeneic HSCT might reduce disease progression, but can be associated with high treatment-related mortality. Thus, we aimed to assess effectiveness of allogeneic HSCT with non-myeloablative conditioning after autologous HSCT compared with tandem autologous HSCT.
METHODS: In our phase 3 biological assignment trial, we enrolled patients with multiple myeloma attending 37 transplant centres in the USA. Patients (
FINDINGS: Between Dec 17, 2003, and March 30, 2007, we enrolled 710 patients, of whom 625 had standard-risk disease and received an autologous HSCT. 156 (83%) of 189 patients with standard-risk disease in the auto-allo group and 366 (84%) of 436 in the auto-auto group received a second transplant. 219 patients in the auto-auto group were randomly assigned to observation and 217 to receive maintenance treatment, of whom 168 (77%) completed this treatment. PFS and overall survival did not differ between maintenance and observation groups and pooled data were used. Kaplan-Meier estimates of 3-year PFS were 43% (95% CI 36-51) in the auto-allo group and 46% (42-51) in the auto-auto group (p=0·671); overall survival also did not differ at 3 years (77% [95% CI 72-84] vs 80% [77-84]; p=0·191). Within 3 years, 87 (46%) of 189 patients in the auto-allo group had grade 3-5 adverse events as did 185 (42%) of 436 patients in the auto-auto group. The adverse events that differed most between groups were hyperbilirubinaemia (21 [11%] patients in the auto-allo group vs 14 [3%] in the auto-auto group) and peripheral neuropathy (11 [6%] in the auto-allo group vs 52 [12%] in the auto-auto group).
INTERPRETATION: Non-myeloablative allogeneic HSCT after autologous HSCT is not more effective than tandem autologous HSCT for patients with standard-risk multiple myeloma. Further enhancement of the graft versus myeloma effect and reduction in transplant-related mortality are needed to improve the allogeneic HSCT approach.
FUNDING: US National Heart, Lung, and Blood Institute and the National Cancer Institute.
|Alternate Journal||Lancet Oncol|
|PubMed Central ID||PMC3611089|
|Grant List||U10 HL069294 / HL / NHLBI NIH HHS / United States |
UG1 HL069286 / HL / NHLBI NIH HHS / United States
U10 HL069301 / HL / NHLBI NIH HHS / United States
U10 HL069330 / HL / NHLBI NIH HHS / United States
U10 HL069291 / HL / NHLBI NIH HHS / United States
U01 HL069294 / HL / NHLBI NIH HHS / United States
P01 CA078902 / CA / NCI NIH HHS / United States
U10 HL069315 / HL / NHLBI NIH HHS / United States
U10 HL069348 / HL / NHLBI NIH HHS / United States
P01 CA018029 / CA / NCI NIH HHS / United States
U10 HL069290 / HL / NHLBI NIH HHS / United States
U24 CA076518 / CA / NCI NIH HHS / United States
U10 HL069286 / HL / NHLBI NIH HHS / United States
U10 HL069249 / HL / NHLBI NIH HHS / United States
U10 HL069334 / HL / NHLBI NIH HHS / United States